An example antibody for use in immunotherapy is Rituximab. Rituximab has specific use in treatment of NLPHL as it is a chimeric monoclonal antibody against the protein CD20. Studies indicate Rituximab offers potential in relapsed or refractory patients, and also in front-line treatment especially in advanced stages. Because of a tendency for relapse, maintenance treatment such as every 6 months for 2 years is suggested. Rituximab has been shown to improve patient outcomes after histological transformation.

There is no consensus regarding the best treatment protocol. Several considerations should be taken into account including age, stage, and prognostic scores (see International Prognostic Index). Patients with advanced disease who are asymptomatic might benefit from a watch and wait approach, as early treatment does not provide survival benefit. When patients are symptomatic, specific treatment is required, which might include various combinations of alkylators, nucleoside analogues, anthracycline-containing chemotherapy regimens (e.g., CHOP), monoclonal antibodies (e.g. rituximab),

radioimmunotherapy, autologous (self) and allogeneic (donor) hematopoietic stem cell transplantation. Follicular lymphoma is regarded as incurable, unless the disease is localized, in which case it can be cured by local irradiation. Although allogeneic stem cell transplantation may be curative, the mortality from the procedure is too high to be a first line option.

In 2010 rituximab was approved by the European Commission for first-line maintenance treatment of follicular lymphoma. Pre-clinical evidence suggests that rituximab could be also used in combination with integrin inhibitors to overcome the resistance to rituximab mediated by stromal cells . However, follicular lymphoma which is CD20 negative will not benefit from Rituximab, which targets CD20.

Trial results released in June 2012 show that bendamustine, a drug first developed in East Germany in the 1960s, more than doubled disease progression-free survival when given along with rituximab. This combination therapy also left patients with fewer side effects than the older treatment (a combination of five drugs—rituximab, cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine and prednisone, collectively called R-CHOP).

There are many recent and current clinical trials for follicular lymphoma. For example, personalised idiotype vaccines have shown promise, particularly as upfront therapy, but have still to prove their efficacy in randomized clinical trials.

Possible options such as anthracycline-containing regimens include ABVD, BEACOPP and CHOP. Results of a trial with COPP/ABV in children suggested positive results with chemotherapy alone are possible without the need for radiation therapy. Optimal chemotherapy is a topic for debate, for example there is evidence of support for treatment with R-CHOP instead of ABVD, results showing high rates (40%) of relapse after 10 years since ABVD chemotherapy. BEACOPP has higher reported toxicity risk.

Radiotherapy is a valid first option for "MALT lymphoma". It provides local control and potential cure in localized gastric stage IE and II 1E disease with 5-year EFS of 85-100% reported in retrospective studies. However, the irradiation field is potentially large as it must include the whole stomach, which can vary greatly in size and shape. Irradiation techniques have improved considerably in the last 20 years, including treating the patient in a fasting state, decreasing the irradiated field and required dose. The moderate dose of 30 Gray (Gy) of involved-field radiotherapy administered in 15 fractions (doses) can be associated with tolerable toxicity and excellent outcomes. Hence, radiotherapy is the preferred approach for local disease where antibiotic therapy has failed, or is not indicated. Evidence also suggests that radiotherapy can be utilized to control localized relapses outside the original radiation field.

Breast implant-associated ALCL is a recently recognized lymphoma and definitive management and therapy is under evaluation. However, it appears that removal of the implant, and resection of the capsule around the implant as well as evaluation by medical and surgical oncologists are cornerstones. Still under evaluation is the extent of capsulectomy: partial versus complete capsulectomy; similarly it is not defined the significance of replacement of the implant in the affected breast, or the removal of contralateral implant. Similarly, the value of radiation therapy and chemotherapy are under evaluation.

Currently, there is a drug, LDK378, undergoing Phase III clinical trials at Vanderbilt University that targets ALK positive small cell lung cancer, and has showed clinical promise in its previous clinical trials. Because approximately 70% of ALCL neoplasms are also ALK positive, there is hope that similar highly selective and potent ALK inhibitors may be used in the future to treat ALK positive cases of ALCL.

The high cure rates and long survival of many patients with Hodgkin's lymphoma has led to a high concern with late adverse effects of treatment, including cardiovascular disease and second malignancies such as acute leukemias, lymphomas, and solid tumors within the radiation therapy field. Most patients with early-stage disease are now treated with abbreviated chemotherapy and involved-field radiation therapy rather than with radiation therapy alone. Clinical research strategies are exploring reduction of the duration of chemotherapy and dose and volume of radiation therapy in an attempt to reduce late morbidity and mortality of treatment while maintaining high cure rates. Hospitals are also treating those who respond quickly to chemotherapy with no radiation.

In childhood cases of Hodgkin's lymphoma, long-term endocrine adverse effects are a major concern, mainly gonadal dysfunction and growth retardation. Gonadal dysfunction seems to be the most severe endocrine long-term effect, especially after treatment with alkylating agents or pelvic radiotherapy.

Patients with early stage disease (IA or IIA) are effectively treated with radiation therapy or chemotherapy. The choice of treatment depends on the age, sex, bulk and the histological subtype of the disease. Adding localised radiation therapy after the chemotherapy regimen may provide a longer progression-free survival compared with chemotherapy treatment alone. Patients with later disease (III, IVA, or IVB) are treated with combination chemotherapy alone. Patients of any stage with a large mass in the chest are usually treated with combined chemotherapy and radiation therapy.

It should be noted that the common non-Hodgkin's treatment, rituximab (which is a monoclonal antibody against CD20) is not routinely used to treat Hodgkin's lymphoma due to the lack of CD20 surface antigens in most cases. The use of rituximab in Hodgkin's lymphoma, including the lymphocyte predominant subtype has been recently reviewed.

Although increased age is an adverse risk factor for Hodgkin's lymphoma, in general elderly patients without major comorbidities are sufficiently fit to tolerate standard therapy, and have a treatment outcome comparable to that of younger patients. However, the disease is a different entity in older patients and different considerations enter into treatment decisions.

For Hodgkin's lymphomas, radiation oncologists typically use external beam radiation therapy (sometimes shortened to EBRT or XRT). Radiation oncologists deliver external beam radiation therapy to the lymphoma from a machine called linear accelerator which produces high energy X Rays and Electrons. Patients usually describe treatments as painless and similar to getting an X-ray. Treatments last less than 30 minutes each.

For lymphomas, there are a few different ways radiation oncologists target the cancer cells. Involved field radiation is when the radiation oncologists give radiation only to those parts of the patient's body known to have the cancer. Very often, this is combined with chemotherapy. Radiation therapy directed above the diaphragm to the neck, chest or underarms is called mantle field radiation. Radiation to below the diaphragm to the abdomen, spleen or pelvis is called inverted-Y field radiation. Total nodal irradiation is when the therapist gives radiation to all the lymph nodes in the body to destroy cells that may have spread.

There is no standard therapy for multicentric Castleman disease. Treatment modalities change based on HHV-8 status, so it is essential to determine HHV-8 status before beginning treatment. For HHV-8-associated MCD the following treatments have been used: rituximab, antiviral medications such as ganciclovir, and chemotherapy.

Treatment with the antiherpesvirus medication ganciclovir or the anti-CD20 B cell monoclonal antibody, rituximab, may markedly improve outcomes. These medications target and kill B cells via the B cell specific CD20 marker. Since B cells are required for the production of antibodies, the body's immune response is weakened whilst on treatment and the risk of further viral or bacterial infection is increased. Due to the uncommon nature of the condition there are not many large scale research studies from which standardized approaches to therapy may be drawn, and the extant case studies of individuals or small cohorts should be read with caution. As with many diseases, the patient's age, physical state and previous medical history with respect to infections may impact the disease progression and outcome.

Most patients with T-cell prolymphocytic leukemia require immediate treatment.

T-cell prolymphocytic leukemia is difficult to treat, and it does not respond to most available chemotherapeutic drugs. Many different treatments have been attempted, with limited success in certain patients: purine analogues (pentostatin, fludarabine, cladribine), chlorambucil, and various forms of combination chemotherapy regimens, including cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), etoposide, bleomycin (VAPEC-B).

Alemtuzumab (Campath), an anti-CD52 monoclonal antibody that attacks white blood cells, has been used in treatment with greater success than previous options. In one study of previously treated people with T-PLL, people who had a complete response to alemtuzumab survived a median of 16 months after treatment.

Some patients who successfully respond to treatment also undergo stem cell transplantation to consolidate the response.

Currently Aggressive NK-cell leukemia, being a subtype of PTCL, is treated similarly to B-cell lymphomas. However, in recent years, scientists have developed techniques to better recognize the different types of lymphomas, such as PTCL. It is now understood that PTCL behaves differently from B-cell lymphomas and therapies are being developed that specifically target these types of lymphoma. Currently, however, there are no therapies approved by the U.S. Food and Drug Administration (FDA) specifically for PTCL. Anthracycline-containing chemotherapy regimens are commonly offered as the initial therapy. Some patients may receive a stem cell transplant. Novel approaches to the treatment of PTCL in the relapsed or refractory setting are under investigation.

For HHV-8-negative MCD (idiopathic MCD), the following treatments have been used: corticosteroids, rituximab, monoclonal antibodies against IL-6 such as tocilizumab and siltuximab, and the immunomodulator thalidomide.

Prior to 1996 MCD carried a poor prognosis of about 2 years, due to autoimmune hemolytic anemia and non-Hodgkin's lymphoma which may arise as a result of proliferation of infected cells. The timing of diagnosis, with particular attention to the difficulty of determining the cause of B symptoms without a CT scan and lymph node biopsy, may have a significant impact on the prognosis and risk of death. Left untreated, MCD usually gets worse and becomes increasingly difficult and unresponsive to current treatment regimens.

Siltuximab prevents it from binding to the IL-6 receptor, was approved by the U.S. Food and Drug Administration for the treatment of multicentric Castleman disease on April 23, 2014. Preliminary data suggest that treatment siltuximab may achieve tumour and symptomatic response in 34% of patients with MCD.

Other treatments for multicentric Castleman disease include the following:

- Corticosteroids

- Chemotherapy

- Thalidomide

Many different anti-cancer drugs are effective for the treatment of AML. Treatments vary somewhat according to the age of the patient and according to the specific subtype of AML. Overall, the strategy is to control bone marrow and systemic (whole-body) disease, while offering specific treatment for the central nervous system (CNS), if involved.

In general, most oncologists rely on combinations of drugs for the initial, "induction phase" of chemotherapy. Such combination chemotherapy usually offers the benefits of early remission and a lower risk of disease resistance. "Consolidation" and "maintenance" treatments are intended to prevent disease recurrence. Consolidation treatment often entails a repetition of induction chemotherapy or the intensification chemotherapy with additional drugs. By contrast, maintenance treatment involves drug doses that are lower than those administered during the induction phase.

Targeted therapy attacks cancer cells at a specific target, with the aim of not harming normal cells.

- Alemtuzumab is a mAb directed against CD52 used in CLL.

- Rituximab, ofatumumab, and obinutuzumab are antibodies against CD20 used to treat CLL.

- Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, is used to treat CLL.

- Idelalisib is a PI3K inhibitor. and is taken orally.

- Venetoclax is a Bcl-2 inhibitor used to treat people with CLL who have 17p deletion (deletion located on the chromosome 17 short arm) and who have been treated with at least one prior therapy.

Combination chemotherapy regimens are effective in both newly diagnosed and relapsed CLL. Combinations of fludarabine with alkylating agents (cyclophosphamide) produce higher response rates and a longer progression-free survival than single agents:

- FC (fludarabine with cyclophosphamide)

- FR (fludarabine with rituximab)

- FCR (fludarabine, cyclophosphamide, and rituximab)

- CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)

Although the purine analogue fludarabine was shown to give superior response rates to chlorambucil as primary therapy, no evidence shows early use of fludarabine improves overall survival, and some clinicians prefer to reserve fludarabine for relapsed disease.

Chemoimmunotherapy with FCR has shown to improve response rates, progression-free survival, and overall survival in a large randomized trial in CLL patients selected for good physical fitness. This has been the first clinical trial demonstrating that the choice of a first-line therapy can improve the overall survival of patients with CLL.

Alkylating agents approved for CLL include bendamustine and cyclophosphamide.

For most people with CLL, it is incurable by present treatments, so treatment is directed towards suppressing the disease for many years, rather than totally and permanently eliminating it. The primary chemotherapeutic plan is combination chemotherapy with chlorambucil or cyclophosphamide, plus a corticosteroid such as prednisone or prednisolone. The use of a corticosteroid has the additional benefit of suppressing some related autoimmune diseases, such as immunohemolytic anemia or immune-mediated thrombocytopenia. In resistant cases, single-agent treatments with nucleoside drugs such as fludarabine, pentostatin, or cladribine may be successful. Younger and healthier patients may choose allogeneic or autologous bone marrow transplantation in the hope of a permanent cure.

"MALT lymphoma" is exquisitely immunotherapy sensitive. Chemotherapy is reserved for those uncommon patients with disseminated disease at presentation or lack of response to local treatment. Rituximab, the anti-CD20 chimeric antibody, is a key component of therapy. Responses vary from 55% to 77% with monotherapy and 100% in combination with chemotherapy. Oral alkylating agents such as cyclophosphamide or chlorambucil have been administered for a median duration of 12 months with high rates of disease control (CR up to 75%) but appear not to be active in t(11;18) disease. The purine nucleoside analogs fludarabine and cladribine also demonstrate activity, the latter conferring a CR rate of 84% (100% in those with gastric primaries) in a small study. A pivotal study of rituximab plus chlorambucil compared with chlorambucil alone (IELSG-19 study, n = 227) demonstrated a significantly higher CR rate (78% vs. 65%; p = 0.017) and 5-year EFS (68% vs. 50%; p = 0.024) over chlorambucil alone. However, 5-year OS was not improved (88% in both arms). First-line treatment of choice is generally rituximab in combination with single alkylating agents or fludarabine, or a combination of all three drugs. The final results of this study, including the later addition of a rituximab-alone arm, are pending.

Two other genetic alterations are known:

- t(1;14)(p22;q32), which deregulates BCL10, at the locus 1p22.

- t(14;18)(q32;q21), which deregulates MALT1, at the locus 18q21.

These seem to turn on the same pathway as API2-MLT (i.e., that of NF-κB). They both act upon IGH, which is at the locus 14q32.

Diffuse large B-cell lymphomas of the stomach are primarily treated with chemotherapy with CHOP (cyclophosphamide+doxorubicine+vincristine+prednisone) with or without rituximab being a usual first choice.

Antibiotic treatment to eradicate H. pylori is indicated as first line therapy for MALT lymphomas. About 60% of MALT lymphomas completely regress with eradication therapy. Radiation treatment for H. pylori negative gastric malt lymphoma, has a high success rate, 90% or better after 5 years. Second line therapy for MALT lymphomas is usually chemotherapy with a single agent, and complete response rates of greater than 70% have been reported.

Subtotal gastrectomy, with post-operative chemotherapy is undertaken in refractory cases, or in the setting of complications, including gastric outlet obstruction.

Alemtuzumab has been investigated for use in treatment of refractory T-cell large granular lymphocytic leukemia.

Several treatments are available, and successful control of the disease is common.

Not everyone needs treatment immediately. Treatment is usually given when the symptoms of the disease interfere with the patient's everyday life, or when white blood cell or platelet counts decline to dangerously low levels, such as an absolute neutrophil count below one thousand cells per microliter (1.0 K/uL). Not all patients need treatment immediately upon diagnosis.

Treatment delays are less important than in solid tumors. Unlike most cancers, treatment success does not depend on treating the disease at an early stage. Because delays do not affect treatment success, there are no standards for how quickly a patient should receive treatment. However, waiting too long can cause its own problems, such as an infection that might have been avoided by proper treatment to restore immune system function. Also, having a higher number of hairy cells at the time of treatment can make certain side effects somewhat worse, as some side effects are primarily caused by the body's natural response to the dying hairy cells. This can result in the hospitalization of a patient whose treatment would otherwise be carried out entirely at the hematologist's office.

Single-drug treatment is typical. Unlike most cancers, only one drug is normally given to a patient at a time. While monotherapy is normal, combination therapy—typically using one first-line therapy and one second-line therapy—is being studied in current clinical trials and is used more frequently for refractory cases. Combining rituximab with cladribine or pentostatin may or may not produce any practical benefit to the patient. Combination therapy is almost never used with a new patient. Because the success rates with purine analog monotherapy are already so high, the additional benefit from immediate treatment with a second drug in a treatment-naïve patient is assumed to be very low. For example, one round of either cladribine or pentostatin gives the median first-time patient a decade-long remission; the addition of rituximab, which gives the median patient only three or four years, might provide no additional value for this easily treated patient. In a more difficult case, however, the benefit from the first drug may be substantially reduced and therefore a combination may provide some benefit.

If a patient is resistant to either cladribine or pentostatin, then second-line therapy is pursued.

Monoclonal antibodies The most common treatment for cladribine-resistant disease is infusing monoclonal antibodies that destroy cancerous B cells. Rituximab is by far the most commonly used. Most patients receive one IV infusion over several hours each week for four to eight weeks. A 2003 publication found two partial and ten complete responses out of 15 patients with relapsed disease, for a total of 80% responding. The median patient (including non-responders) did not require further treatment for more than three years. This eight-dose study had a higher response rate than a four-dose study at Scripps, which achieved only 25% response rate. Rituximab has successfully induced a complete response in Hairy Cell-Variant.

Rituximab's major side effect is serum sickness, commonly described as an "allergic reaction", which can be severe, especially on the first infusion. Serum sickness is primarily caused by the antibodies clumping during infusion and triggering the complement cascade. Although most patients find that side effects are adequately controlled by anti-allergy drugs, some severe, and even fatal, reactions have occurred. Consequently, the first dose is always given in a hospital setting, although subsequent infusions may be given in a physician's office. Remissions are usually shorter than with the preferred first-line drugs, but hematologic remissions of several years' duration are not uncommon.

Other B cell-destroying monoclonal antibodies such as Alemtuzumab, Ibritumomab tiuxetan and I-131 Tositumomab may be considered for refractory cases.

Interferon-alpha Interferon-alpha is an immune system hormone that is very helpful to a relatively small number of patients, and somewhat helpful to most patients. In about 65% of patients, the drug helps stabilize the disease or produce a slow, minor improvement for a partial response.

The typical dosing schedule injects at least 3 million units of Interferon-alpha (not pegylated versions) three times a week, although the original protocol began with six months of daily injections.

Some patients tolerate IFN-alpha very well after the first couple of weeks, while others find that its characteristic flu-like symptoms persist. About 10% of patients develop a level of depression. It is possible that, by maintaining a steadier level of the hormone in the body, that daily injections might cause fewer side effects in selected patients. Drinking at least two liters of water each day, while avoiding caffeine and alcohol, can reduce many of the side effects.

A drop in blood counts is usually seen during the first one to two months of treatment. Most patients find that their blood counts get worse for a few weeks immediately after starting treatment, although some patients find their blood counts begin to improve within just two weeks.

It typically takes six months to figure out whether this therapy is useful. Common criteria for treatment success include:

- normalization of hemoglobin levels (above 12.0 g/dL),

- a normal or somewhat low platelet count (above 100 K/µL), and

- a normal or somewhat low absolute neutrophil count (above 1.5 K/µL).

If it is well tolerated, patients usually take the hormone for 12 to 18 months. An attempt may be made then to end the treatment, but most patients discover that they need to continue taking the drug for it to be successful. These patients often continue taking this drug indefinitely, until either the disease becomes resistant to this hormone, or the body produces an immune system response that limits the drug's ability to function. A few patients are able to achieve a sustained clinical remission after taking this drug for six months to one year. This may be more likely when IFN-alpha has been initiated shortly after another therapy. Interferon-alpha is considered the drug of choice for pregnant women with active HCL, although it carries some risks, such as the potential for decreased blood flow to the placenta.

Interferon-alpha works by sensitizing the hairy cells to the killing effect of the immune system hormone TNF-alpha, whose production it promotes. IFN-alpha works best on classic hairy cells that are not protectively adhered to vitronectin or fibronectin, which suggests that patients who encounter less fibrous tissue in their bone marrow biopsies may be more likely to respond to Interferon-alpha therapy. It also explains why non-adhered hairy cells, such as those in the bloodstream, disappear during IFN-alpha treatment well before reductions are seen in adhered hairy cells, such as those in the bone marrow and spleen.

Due to the high risk of recurrence and ensuing problems, close monitoring of dogs undergoing chemotherapy is important. The same is true for dogs that have entered remission and ceased treatment. Monitoring for disease and remission/recurrence is usually performed by palpation of peripheral lymph nodes. This procedure detects gross changes in peripheral lymph nodes. Some of the blood tests used in diagnosing lymphoma also offer greater objectivity and provide an earlier warning of an animal coming out of remission.

Complete cure is rare with lymphoma and treatment tends to be palliative, but long remission times are possible with chemotherapy. With effective protocols, average first remission times are 6 to 8 months. Second remissions are shorter and harder to accomplish. Average survival is 9 to 12 months. The most common treatment is a combination of cyclophosphamide, vincristine, prednisone, L-asparaginase, and doxorubicin. Other chemotherapy drugs such as chlorambucil, lomustine (CCNU), cytosine arabinoside, and mitoxantrone are sometimes used in the treatment of lymphoma by themselves or in substitution for other drugs. In most cases, appropriate treatment protocols cause few side effects, but white blood cell counts must be monitored.

Allogeneic and autologous stem cell transplantations (as is commonly done in humans) have recently been shown to be a possible treatment option for dogs. Most of the basic research on transplantation biology was generated in dogs. Current cure rates using stem cell therapy in dogs approximates that achieved in humans, 40-50%.

When cost is a factor, prednisone used alone can improve the symptoms dramatically, but it does not significantly affect the survival rate. The average survival times of dogs treated with prednisone and untreated dogs are both one to two months. Using prednisone alone can cause the cancer to become resistant to other chemotherapy agents, so it should only be used if more aggressive treatment is not an option.

Isotretinoin can be used to treat cutaneous lymphoma.

When primary or secondary resistance invariably develops, salvage therapy is considered. Allogeneic stem cell transplantation can induce durable remissions for heavily pre-treated patients.

Should treatment be started it should address both the paraprotein level and the lymphocytic B-cells.

In 2002, a panel at the International Workshop on Waldenström's Macroglobulinemia agreed on criteria for the initiation of therapy. They recommended starting therapy in patients with constitutional symptoms such as recurrent fever, night sweats, fatigue due to anemia, weight loss, progressive symptomatic lymphadenopathy or spleen enlargement, and anemia due to bone marrow infiltration. Complications such as hyperviscosity syndrome, symptomatic sensorimotor peripheral neuropathy, systemic amyloidosis, kidney failure, or symptomatic cryoglobulinemia were also suggested as indications for therapy.

Treatment includes the monoclonal antibody rituximab, sometimes in combination with chemotherapeutic drugs such as chlorambucil, cyclophosphamide, or vincristine or with thalidomide. Corticosteroids, such as prednisone, may also be used in combination. Plasmapheresis can be used to treat the hyperviscosity syndrome by removing the paraprotein from the blood, although it does not address the underlying disease. Ibrutinib is another agent that has been approved for use in this condition.

Recently, autologous bone marrow transplantation has been added to the available treatment options.

Treatment with conventional immunochemotherapy is usually indicated; in younger patients, allogeneic bone marrow transplantation may be curative.

Treatment with chemotherapy has been used with some success, particularly using lomustine, prednisone, doxorubicin, and cyclophosphamide. Because of the rapid progression of this aggressive disease, the prognosis is very poor.